Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?

Feng Li, Yiping Shen, Udo Köhler, Freddie H. Sharkey, Deepa Menon, Laurence Coulleaux, Valérie Malan, Marlène Rio, Dominic J. McMullan, H. Cox, Kerry A. Fagan, Lorraine Gaunt, Kay Metcalfe, Uwe Heinrich, Gordon Hislop, Una Maye, Maxine Sutcliffe, Bai Lin Wu, Brian D. Thiel, Surabhi Mulchandani & 4 others Laura K. Conlin, Nancy B. Spinner, Kathleen M. Murphy, Denise A S Batista

Research output: Contribution to journalArticle

Abstract

The use of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays has dramatically altered the approach to identification of genetic alterations that can explain intellectual disability and /or congenital anomalies. However, the discovery of numerous copy number changes with benign or unknown clinical significance has made interpretation problematic. Submicroscopic duplication of Xp22.31 has been reported as either a possible cause of intellectual disability and/or developmental delay or a benign variant. Here we report 29 individuals with the microduplication found as part of microarray analysis of 7793 samples submitted to an international group of 13 clinical laboratories. The referral reasons varied and included developmental delay, intellectual disability, autism, dysmorphic features and/or multiple congenital anomalies. The size of the Xp22.31 duplication varied between 149 kb and 1.74 Mb and included the steroid sulfatase (STS) gene with the male to female ratio of 0.7. Duplication within this segment is seen at a frequency of 0.15% in a healthy control population, whereas a frequency of 0.37% was observed in our cohort of individuals with abnormal phenotypes. We present a detailed comparison of the breakpoints, inheritance, X-inactivation and clinical phenotype in our cohort and a review of the literature for a total of 41 patients. To date, this report is the largest compilation of clinical and array data regarding the microduplication of Xp22.31 and will serve to broaden the knowledge of regions involving copy number variation (CNV).

Original languageEnglish (US)
Pages (from-to)93-99
Number of pages7
JournalEuropean Journal of Medical Genetics
Volume53
Issue number2
DOIs
StatePublished - Mar 2010

Fingerprint

Intellectual Disability
Phenotype
Steryl-Sulfatase
X Chromosome Inactivation
Comparative Genomic Hybridization
Microarray Analysis
Autistic Disorder
Single Nucleotide Polymorphism
Referral and Consultation
Genes

Keywords

  • Autism
  • Behavior problems
  • CNV
  • Intellectual disability
  • Microarray
  • Microdeletion
  • SNP
  • STS
  • Xp22.31

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Interstitial microduplication of Xp22.31 : Causative of intellectual disability or benign copy number variant? / Li, Feng; Shen, Yiping; Köhler, Udo; Sharkey, Freddie H.; Menon, Deepa; Coulleaux, Laurence; Malan, Valérie; Rio, Marlène; McMullan, Dominic J.; Cox, H.; Fagan, Kerry A.; Gaunt, Lorraine; Metcalfe, Kay; Heinrich, Uwe; Hislop, Gordon; Maye, Una; Sutcliffe, Maxine; Wu, Bai Lin; Thiel, Brian D.; Mulchandani, Surabhi; Conlin, Laura K.; Spinner, Nancy B.; Murphy, Kathleen M.; Batista, Denise A S.

In: European Journal of Medical Genetics, Vol. 53, No. 2, 03.2010, p. 93-99.

Research output: Contribution to journalArticle

Li, F, Shen, Y, Köhler, U, Sharkey, FH, Menon, D, Coulleaux, L, Malan, V, Rio, M, McMullan, DJ, Cox, H, Fagan, KA, Gaunt, L, Metcalfe, K, Heinrich, U, Hislop, G, Maye, U, Sutcliffe, M, Wu, BL, Thiel, BD, Mulchandani, S, Conlin, LK, Spinner, NB, Murphy, KM & Batista, DAS 2010, 'Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?' European Journal of Medical Genetics, vol 53, no. 2, pp. 93-99. DOI: 10.1016/j.ejmg.2010.01.004

Li, Feng; Shen, Yiping; Köhler, Udo; Sharkey, Freddie H.; Menon, Deepa; Coulleaux, Laurence; Malan, Valérie; Rio, Marlène; McMullan, Dominic J.; Cox, H.; Fagan, Kerry A.; Gaunt, Lorraine; Metcalfe, Kay; Heinrich, Uwe; Hislop, Gordon; Maye, Una; Sutcliffe, Maxine; Wu, Bai Lin; Thiel, Brian D.; Mulchandani, Surabhi; Conlin, Laura K.; Spinner, Nancy B.; Murphy, Kathleen M.; Batista, Denise A S / Interstitial microduplication of Xp22.31 : Causative of intellectual disability or benign copy number variant?

In: European Journal of Medical Genetics, Vol. 53, No. 2, 03.2010, p. 93-99.

Research output: Contribution to journalArticle

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